DESCRIPTION: (Adapted from applicant's description): Polycystic ovary syndrome (PCOS) is a disorder affecting about 5% of reproductive-age women characterized by anovulation and excess production of androgens by the ovary. Anovulation causes menstrual irregularity and infertility, while excess androgens cause unwanted hair growth and may promote acne. Traditional treatments for PCOS have consisted of medication to stimulate ovulation if fertility is desired, or medication to suppress or block androgents or restore regular menstrual cycles if fertility is not an immediate goal, but these treatments are often mutually exclusive PCOS is frequently associated with a common metabolic disorder, insulin resistance, and like insulin resistance alone carries an increased risk of non-reproductive health problems such as the development of diabetes or atherosclerosis. Insulin resistance leads to excessive insulin secretion, and this may stimulate the ovary to hypersecrete androgens. In the last few years, published reports have described the treatment of PCOS with insulin sensitizers, medications developed to treat diabetes which can improve insulin resistance. These drugs can improve the hormonal abnormalities in PCOS and in some cases can restore regular menses and/or ovulation. Of the two marketed drugs tested to date, metformin has not been consistently effective, while troglitazone is effective but has been found to have an unacceptable risk of liver toxicity. This project will study rosiglitazone, a newly approved drug closely related to troglitazone in structure and action but without apparent toxicity, in an open-label, Phase II format. Subjects with PCOS wiII have insulin resistance identified by dynamic testing using the octreotide insulin suppression test, and after further evaluation of provoked insulin secretion will receive rosiglitazone daily in one of three doses for 12 weeks. Insulin resistance and insulin secretion, glucose tolerance, serum total and free testosterone, LH, and circulating lipids will be measured on rosiglitazone and compared to subjects' pretreatment values. The occurrence of ovulation will be evaluated by weekly serum progesterone levels. The dose of rosiglitazone and the time needed for its effect to develop will be determined. Associations between effects on metabolic parameters and effects on reproductive ones will be sought. The hypothesis of this study is that rosiglitazone can improve insulin sensitivity and lower circulating insulin, and thereby restore ovulation as well as correct elevated LH and testosterone. Rosiglitazone is potentially an appropriate and beneficial treatment for all women with PCOS and insulin resistance regardless of goals.